Sodium Methoxide → (R)-methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

HRID 1055110Notes

Reaction equation

HRID 1055110 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([F:43])[C:6]([NH:29][CH:30]([C:37]2([CH3:42])[CH2:41][CH2:40][CH2:39][CH2:38]2)[CH2:31][C:32]([O:34][CH2:35]C)=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[N:11](S(C2C=CC(C)=CC=2)(=O)=O)[CH:10]=1)#[N:2].C(C1C=C(F)C(N[C@@H](C2(C)CCCC2)CC(OCC)=O)=NC=1C1C2C(=NC=C(F)C=2)N(S(C2C=CC(C)=CC=2)(=O)=O)C=1)#N.C[O-].[Na+]>C1COCC1.C([O-])(O)=O.[Na+].CCOC(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([F:43])[C:6]([NH:29][C@@H:30]([C:37]2([CH3:42])[CH2:38][CH2:39][CH2:40][CH2:41]2)[CH2:31][C:32]([O:34][CH3:35])=[O:33])=[N:7][C:8]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([F:18])[CH:16]=2)[NH:11][CH:10]=1)#[N:2]

Participants

7

Reactant 3

HCID 10942334Sodium MethoxideHCID 71247912racemic ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoateHCID 86714768(R)-ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

Product 1

HCID 71247738(R)-methyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of racemic ethyl 3-(5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-ylamino)-3-(1-methylcyclopentyl)propanoate, 144a, (0.150 g, 0.247 mmol) in THF (20 mL) was added sodium methoxide (0.053 mL of 25% wt solution in MeOH, 0.247 mmol). The reaction mixture was stirred at room temperature for 5 minutes. The reaction mixture was diluted with aqueous saturated NaHCO3 solution and EtOAc. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The product was purified by silica gel chromatography (40% EtOAc/Hexanes) to afford 90 mg of the desired product as a mixture of ethyl and methyl esters. The mixture was taken onto the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 10.18 (s, 1H), 8.65 (dd, J=9.6, 2.5 Hz, 1H), 8.48 (d, J=2.8 Hz, 1H), 8.32 (s, 1H), 7.37 (t, J=14.1 Hz, 1H), 5.38 (d, J=7.9 Hz, 1H), 5.02 (td, J=9.8, 3.5 Hz, 1H), 3.54 (s, 3H), 2.80 (dt, J=15.8, 7.9 Hz, 1H), 2.57 (dd, J=14.9, 9.8 Hz, 1H), 1.80-1.57 (m, 7H), 1.43 (ddd, J=24.5, 14.1, 6.0 Hz, 3H), 1.08 (s, 3H); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=3.60 minutes (M+H) 440.26.

Workup

  1. dry with materialThe organic phase was dried over MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe product was purified by silica gel chromatography (40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-785a92b415aa4c7b9d3980f7418f5368
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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